On Wednesday, we blogged about the innovative proposals put forth by the Food and Drug Administration Transparency Task Force regarding drug safety, which we commented on.  The initiatives are part of the FDA’s three-phase effort to increase Agency transparency, an effort that Community Catalyst fully supports.  Today, we look at what consumer advocates, health professionals, and the pharmaceutical industry said about these potential reforms.

The overwhelming response to these proposals has been positive. Across the spectrum, disparate organizations from the drug industry trade group PhRMA to the consumer watch dog group Public Citizen voiced their support for movement toward a more transparent FDA. As the Advanced Medical Technology Association (AdvaMed) stated in comments, “greater transparency in FDA operations is a desirable goal.”  However, as always, the devil is in the detail. There was disagreement over the types of disclosures that would best serve the public and just how much transparency is enough. Here are three issues that were most prominently commented upon, illustrating the accord and dissent among the groups.

Proprietary Research versus Proper Research

Public Citizen and some other consumer groups issued comments generally aligned with ours, praising the Task Force’s proposals, and offering additional steps the Agency should take toward useful transparency.  Like us, Public Citizen urged the FDA to release all summary safety and efficacy data from pre-approval and marketing applications. The group points out that despite industry claims, releasing summary data would not harm firms, citing a Task Force finding that “industry has not demonstrated that blanket protection of aggregate information is warranted to maintain incentives for innovation.” Instead, Public Citizen explains, “release of all summary safety and efficacy data is in the interest of public health, because it enhances scientific innovation and discovery.” Beyond the clear safety benefits of releasing the raw clinical data, which we outlined Wednesday, Public Citizen makes a compelling case that such disclosures are legal, citing legal victories that they have won over the years to establish that, absent some proof that a competitor would gain an advantage, “generally . . . clinical data submitted to FDA is not confidential commercial information.” More public access to data on drug safety research, not less, benefits us all.

Adverse Event Reporting

While industry and consumer groups differed on how much data should be disclosed and in what format, the groups generally supported the Task Force proposal to increase public access to and user-friendliness of information on adverse events associated with drugs. PhRMA, AdvaMed and others also noted the importance of disclaimer information that should be provided along with adverse events data. This is a concern we share – and commented on. Ensuring that the public understands and can make use of the newly accessibly data should be a priority.

Many groups also welcomed the transparency proposals for their anticipated effect on the Freedom of Information Act process. The American Association for Justice wrote that the additional disclosures the Initiative would, particularly in regards to adverse event information, “relieve some of the burden on the FDA FOIA office and allow them to complete other requests in a more timely fashion.” How significant is this burden? Public Citizen notes that even after spending $29 million in 2009 handling FOIA requests, there remained a ‘backlog’ of 4,818 FOIA requests at the end of 2009 fiscal year (September 30, 2009).

Prescribers, too, want better access to this information. The American College of Cardiology (ACC) said the disclosures would greatly benefit practitioners who depend on accurate adverse event information to guide their prescribing practices. “Medical professionals, such as practicing cardiologists, are unlikely to go through the time, expense and hassle of filing a Freedom of Information Act (FOIA) request to obtain this information,” the ACC commented. “Providing the information without the need for FOIA requests will reduce the number of FOIA requests, thus decreasing FDA expenses in this area.” ACC also noted that a more open adverse events data system would encourage doctors to report more of the events that occur among their patients, building a better database that stands to benefit us all.

Recall Authority

Many consumer and professional groups raised concerns over the FDA’s lack of drug recall authority. Recent events, including an unofficial, “phantom recall” of some Johnson & Johnson products and another incident resulting in the recall of over 130 million bottles of common over-the-counter children’s medications, have no doubt focused public attention on FDA’s current lack of authority to initiate a recall, as well as limited requirements for manufacturers to notify FDA of drug safety and quality issues. We are supportive of proposals 18, 19 and 20, because they would help to eliminate the uncertainty that has often shrouded industry practices and sometimes even FDA actions around issues of drug safety.

We have long supported expanded authority for FDA to require a drug recall when patient safety is at risk, and it is becoming clear that a growing number of groups have adopted similar positions. The Academy of Managed Care Pharmacy supported the Task Force’s proposal to seek authority to require manufacturers and distributors to inform the Agency when they initiate a recall. This would likely help avoid another “phantom recall.” The Academy goes on to encourage the FDA to expand its authority even further and pursue legislative power to initiate the recall of medications. The group added that “Patient safety should be the primary concern of the FDA, and legislative authority to initiate the recall of medications is necessary to allow action to ensure the safe use of medications.” The American Society of Health-System Pharmacists asserted that improving the recall process should be an FDA priority and outlined a standard recall notification process that the FDA should develop as the Agency is “in the best position to ensure that useful, actionable information is provided to the public if a problem arises with an FDA-regulated product.”

While the FDA proposals and comments cover many more components of the FDA’s transparency initiative, all of which are important in improving the safety of prescription drugs, the comments highlighted here remind us that there is a general consensus among consumer, professional and—to some extent—industry groups in a call for greater transparency. The FDA has taken a proactive approach to transparency and provided for an open process that allows everyone’s voice to be heard. We look forward to seeing the outcome of Phase II, when the Transparency Task Force will consider public comments and make its final recommendations to Commissioner Hamburg.

– Joy Lee, Policy Intern

The Food and Drug Administration will soon complete the second stage of a three-phase process to increase public transparency of agency activities and decision making. Last week, the FDA’s new Transparency Task Force concluded a three-month comment period on 21 bold new proposals to expand the agency’s disclosure practices. Community Catalyst, with the support of prominent drug safety experts Drs. Joseph Ross and Aaron Kesselheim of Yale University Medical Center and Harvard Medical School, respectively, filed comments endorsing many of these proposals with respect to prescription drugs, and recommending other improvements to promote public health and empower patients and consumers.

Seeing Clearly Now – The Importance of Transparency

The FDA task forces sees increased transparency as part of new Administration’s Open Government Initiative, and as a means to build public confidence in the FDA by making the agency’s activities and decision-making more accessible and understandable to consumers, providers and other public health experts. These 21 proposals would significantly increase access to information in nearly all areas of prescription drug regulation, from developmental studies to inspections of manufacturing and import procedures to adverse reactions experienced by patients.

Many of these common sense proposals are especially timely in light of the recent revelations about drug makers withholding critical information about drug safety studies and manufacturing problems.

For instance, the FDA recently made public a report summarizing 12 manufacturing violations and other inspection findings concerning a Johnson and Johnson plant in Lancaster, Pennsylvania. This is notable as it was the third Johnson and Johnson plant to be cited for violations this year, the same year in which the company has recalled over 130 million bottles of children’s medication due to possible contamination. A congressional investigation recently found that in June 2009 the company’s McNeil division sent in contractors to surreptitiously buy up potentially contaminated Motrin, rather than issue a formal recall of the product. One new transparency reform being considered by FDA would make information on inspections and violations at manufacturing facilities open to the public. This would inform consumers about when FDA uncovers problems in the manufacturing process—or when a company has a clean record. Increased public scrutiny of problematic industry manufacturing practices will alert consumers when problems arise, and also help force manufacturers to prioritize quality improvement.

Also of great interest to the drug safety and patient community are the proposed disclosures of the status of product applications and the release of summary clinical trial data on drug safety and effectiveness. Such information would notify patients awaiting the development of new drugs on the industry’s efforts and safety concerns and help prescribers make informed decisions. Most importantly, the disclosure would also allow independent researchers to conduct their analyses in order to complement FDA and industry research.

The recent revelations that GlaxoSmithKline withheld studies documenting the cardiac risks associated with their blockbuster drug Avandia, and selectively excluded negative data from other published studies demonstrates the need for full transparency.

GSK’s actions were nearly identical to drug maker Merck’s withholding of studies documenting the cardiac risks of Vioxx, which is estimated to be responsible for tens of thousands of heart attacks. In both cases, lack of access to this data meant that it took years for the health risks of these products to come to light.

Even so, under the current scheme, FDA sits atop a mountain of clinical data submitted with marketing applications that may help identify risks sooner. Had comprehensive clinical trial data on Vioxx and Avandia been available to independent researchers earlier, health risks associated with these drugs could have been discovered and publicized much earlier. Lives could have been saved. The FDA simply does not have the resources to perform all the analyses that independent investigators can.

These safety issues, coupled with recent manufacturing problems that have undermined the integrity of our drug supply chain, demonstrate the need for expanded FDA disclosure of drug approval information and inspection results.

Will it be a Bright Sun Shiny Day?

Aside from supporting the FDA’s bold new approach to increase transparency, we also recommended that the FDA go farther in some areas. For instance, we feel that the FDA’s proposal to disclose the scope and completion of a food recall be expanded to include any recall of prescription drugs, as well.

And while the FDA has proposed future meetings to discuss the disclosure of non-summary (or individual level) data from drug trials, we argued that the need for public access to this data is beyond dispute because it allows independent researchers to more quickly complete objective drug safety analyses that reveal risks and thus sound the alarm on patient safety issues.

(Tune in tomorrow to learn what other consumer advocate, and the drug industry said about these vital transparency reforms.)

– Ian Reynolds, Policy Associate
– Joy Lee, Policy Intern

Yesterday, Harvard Medical School announced strict conflict-of-interest rules that limit ties between its 11,000 faculty members and pharmaceutical and medical device makers, making it one of a growing number of medical schools across the country to address concerns about the influence of industry marketing on the education, training and practice of physicians.

Highlights of the new policy, which will be phased in by January 1, 2011, include:

• prohibiting all personal gifts, travel or meals from industry
• banning participation on speakers bureaus (company-controlled talks)
• capping at $10,000 annually per company the amount faculty can earn from a company whose technology or product they are investigating in clinical research
• requiring Harvard to post on its website faculty member financial interests in, or payments from, pharmaceutical and medical device companies
• prohibiting companies from sponsoring specific Harvard-run CME courses for physicians, unless more than one company sponsors the course and no one company funds more than 50 percent
• requiring industry exhibits and programs to be held at a separate time and place from Harvard CME courses

As one of the world’s most prestigious medical education and research institutions, Harvard’s decision to strengthen its rules is a powerful acknowledgement of the impact of aggressive industry marketing on medicine. It also sends a strong signal to other institutions that have yet to address industry’s presence on medical campuses. It is also a reminder to the Massachusetts legislature, which is debating efforts to repeal the state’s ban on industry gifting to prescribers, that the medical profession is increasingly embracing the need for these restrictions and ethical standards.

When the Prescription Project formed in 2007 with a goal of eliminating conflicts of interest at academic medical centers, conventional wisdom had it that change at Harvard and its affiliated hospitals would not come easily. After Boston University and UMass Memorial Medical Center released strong policies in 2007 and 2008 respectively, the Project convened all of the Boston-based academic medical centers with the hopes of building momentum for change at all of the Massachusetts-based schools and teaching hospitals.

Harvard’s new policy buttresses similar guidelines issued last year by Partners Healthcare, which employs thousands of Harvard physicians and operates two of Harvard’s teaching hospitals – Mass General and Brigham & Women’s.

As a number of other top institutions around the country – Stanford, University of Pittsburgh, University of California Davis – released new COI policies in 2008 and 2009, attention continued to focus on Harvard. A series of unflattering media exposés on Harvard physicians’ ties to industry, followed by a Congressional investigation by Senator Charles Grassley (R-Iowa) into whether the physicians had violated federal conflict-of-interest payments for failure to disclose large drug company payments, raised questions about the school’s policy and helped thrust the issue into the national spotlight.

In June of 2008, the American Medical Student Association (AMSA) released its Pharmfree Scorecard developed in partnership with the Pew Prescription Project. Harvard received an “F” score due to its failure to submit its policy. The score garnered unwanted media attention from several major national news outlets.

In addition to creating external pressure on Harvard, AMSA began to work internally to push for reform and signs of progress were beginning to surface. When the Harvard University Faculty of Medicine Committee on Conflicts of Interest and Commitment convened in late 2008, AMSA members from Harvard Medical School and across New England asked for involvement in the policy drafting process, increased transparency, mandatory lecturer disclosure and a reasonable timeline for drafting and implementation.

Last year, Harvard submitted policies to AMSA and received a “B” score on the 2009 Pharmfree Scorecard.

“Harvard’s policy represents an important milestone because many institutions look to Harvard to set an example,” said Chris Manz, Pharmfree Director at AMSA.  “While the policy revision has room for improvement, it sends the message that academic medical centers can responsibly collaborate with industry while also preserving the integrity of the medical practice, and we’re proud that PharmFree students played an integral role in its development”

In some areas, Harvard’s new rules may set standards for other schools, particularly in the area of faculty earnings from industry. The rules cap at $10,000 the amount Harvard faculty can earn from a company whose technology or product they are investigating in clinical research.

Despite that, the new rules on continuing medical education (CME) do not go as far as those at schools like UMass and Stanford, which the Project has cited as model policies. Nevertheless, it will be interesting to see how the CME policies impact Pri-Med, the Boston-based annual physicians conference that features Harvard lecturers and has been a carnival of industry marketing. The new rules propose a “firewall” between Harvard and the companies that use these events to market their wares in every spot imaginable, including, apparently, the bathrooms, which will no longer be allowed.

Overall, these are strong policies that will be hugely influential.

– Kathy Melley, Director of Communications

It’s been a rough couple of weeks for GlaxoSmithKline. On the eve of last week’s FDA hearings to decide whether its former best-selling diabetes drug Avandia should still be sold, the New York Times broke news of the company’s efforts to conceal internal studies showing the drug posed a much higher risk of heart attack than its main brand-name competitor, Actos. Yesterday, we learned that a member of the FDA panel received payments from GSK. And, today, the FDA put the brakes on a new trial to compare Avandia with Actos (hat tip: Pharmalot).

But buried in the onslaught of Avandia news (perhaps on purpose?) was the PR-challenged drugmaker’s announcement last Friday that “a small number” of Advair diskus inhalers, (used to treat patients with asthma and chronic obstructive pulmonary disease) stolen from a company warehouse had made their way into pharmacies. GSK’s announcement was followed by a stern FDA warning to consumers, pharmacists, and wholesalers to cease use of the stolen inhalers, which are identifiable by lot numbers.

This story is a troubling reminder that we do not have strong systems in place in this country to ensure our drugs have traveled legitimate and safe routes during distribution. As Adam Fein points out in yesterday’s Drug Channel blog, these stolen products ended up on pharmacy shelves due to negligent purchasing. Someone involved in the distribution of these inhalers purchased diverted products from a bad actor, either knowingly or by not adequately verifying product provenance.

We need strong federal regulation requiring manufacturers, wholesalers and pharmacies to track drugs during distribution and verify products’ distribution histories, also known as “drug pedigrees.” A robust federal tracking regulation with strong drug pedigree standards would help protect consumers from unsafe products. A number of state pedigree laws exist but vary in strength. Two bills have been introduced in the House that would establish federal drug tracking systems:

H.R.2726: Counterfeit Drug Enforcement Act of 2009 (Tim Fagan Law)
Sponsors: Rep. Israel, Rep. Ackerman

H.R. 5839: The Safeguarding America’s Pharmaceuticals Act of 2008 (expected to be reintroduced this session)
Sponsors: Rep. Buyer, Rep. Matheson

We hope this latest disturbing incident serves as another stark reminder of the urgent need for Congress and the FDA to take action to address the safety gaps in the drug distribution system. As for GSK and other manufacturers—they need to beef up their security, let the public and FDA know immediately when it is breached, and embrace proposed new tracking systems.

For more on drug safety and the importance of developing a prescription drug tracking system, visit the Pew Prescription Project’s Securing a Safe Drug Supply.

– Kathy Melley, Director of Communications

Last week’s article by New York Times reporter Gardiner Harris exposed Glaxo SmithKline’s (GSK) flagrant disregard for patient safety. For 11 years GSK suppressed internal studies showing that the world’s former best selling diabetes drug, Avandia, posed a much higher risk of heart attack than its main brand-name competitor, Actos.

Last Wednesday, an FDA advisory review panel concluded a two-day hearing by recommending 20 to 12 that Avandia remain on the market with label revisions and other restrictions. This deeply divided panel included 17 votes to add warnings or restrictions on the drug, and 12 votes to remove the drug from the market.

The members voting for Avandia’s removal said the drug “has no unique benefits and therefore the benefits of the drug do not outweigh the risks.” They also pointed out that Avandia’s primary competitor, Actos, is an acceptable alternative to Avandia and therefore there is no therapeutic necessity to keep Avandia on the market.

Even the use of Actos has been called into question. Harvard researchers based at the Independent Drug Information Service (www.RxFacts.org), note that “in mid-2007 the FDA added black-box warnings cautioning that both rosiglitazone (Avandia) and pioglitazone (Actos) increase the risk of congestive heart failure. These safety concerns, along with an increased risk of fracture, have greatly dampened enthusiasm for use of both of these drugs.

The ultimate fate of Avandia now rests in the hands of the FDA. If the proposed additional warnings and restrictions are implemented, scientist Steve Nissen, who published the first study documenting the cardiac risks of Avandia in 2007, estimates that 95 percent of Avandia’s use will end. “Effectively, this drug is gone.”

Interestingly, the committee also recommended by a vote of 19-11 that the trial currently underway comparing Avandia to its rival Actos be continued, though at least one member questioned the ethics of this, given the potential risks.

The Phantom 1999 Study

We now know that GSK conducted a 1999 study comparing Avandia to its main competitor, Actos, that linked Avandia to a 43 percent increased risk of heart attacks. GSK never reported these findings to the FDA. An email from Dr. Martin I. Freed, a GSK executive at that time said:

Per Sr. Mgmt request, these data should not see the light of day to anyone outside of GSK.

When another GSK official asked whether this trial and another negative study should be published, Freed responded: “Not a chance. These put Avandia in quite a negative light… [W]e would hope that these do not see the light of day.”
Other company documents reveal that in the 1990s, GSK decided against doing another study to determine definitively whether Avandia caused heart attacks because it feared that the results might hurt sales.

Litigation yields access to studies, helps expose risks

GSK’s earlier suppression of studies showing risks associated with the anti-depressant drug Paxil led to litigation and settlements that required GSK to post information online about all their clinical trials. Using this and other information, researchers Nissen and Kathy Wolski of the Cleveland Clinic published in 2007 an analysis of over 40 studies showing that Avandia increased the risk of heart attack, stroke and death in comparison to rival drug Actos.

GSK responded to the Nissen study by publishing results from their own  six-year ‘RECORD’ study. At the time, GSK asserted the RECORD study proved that Avandia posed no increased risk of heart attack or death. But reviewers have found a dozen serious incidents were excluded in the total tally of adverse events from the RECORD study. According to one FDA reviewer, “deaths that occurred while taking Avandia were inexplicably dropped from the final analysis.” Now GSK’s possible role in manipulating the RECORD study to keep their drug on the market is in question.

New evidence, studies bring risks to light

Ongoing investigations by Senator Grassley and almost a dozen new studies documenting the risks of Avandia have kept the issue alive, prompting the FDA’s ongoing review, including last week’s hearing.

One comparative effectiveness study by David Graham of the FDA was published this past June. Graham worked with researchers at the Centers for Medicare and Medicaid Services to collect records from nearly a quarter million Medicare recipients.  Elderly diabetics, who used Avandia instead of its competitor Actos, had a 68 percent increase in the risk of heart attack, stroke, heart failure or death. Graham stated:

We estimate that about 48,000 excess cases of [heart attack], stroke, heart failure, or death were attributable to the use of [Avandia] rather than [Actos] from 1999-2009.

Graham additionally stated “the RECORD study would have been dismissed as ’garbage’ if it had been used to seek the drug’s original approval.”

What’s next?

Whether the FDA will allow Avandia will remain on the market is still in question.  Beyond that, what else can we do to stop such illegal and hazardous industry behavior – the same behavior that resulted in the Vioxx tragedy, which led to up to 60,000 deaths? Litigation and other sources have revealed the suppression of drug risks concerning Vioxx, Paxil, Celexa, Zyprexa, and many other drugs. The problem seems endemic.

To begin to address this problem, FDA needs the resources and authority to examine all relevant clinical studies for data-tampering. Government and private consumer lawsuits must continue, including possible criminal prosecution. Finally, we should all remember that what you read on your drug label or hear in a TV ad may not be the whole story. Skepticism is warranted and further regulation is critical to all of us – we need medical care we can trust.

– Emily Cutrell, Prescription Access Litigation

At a time when state fiscal woes are forcing cuts in Medicaid, researchers at the Division of Pharmacoepidemiology at Brigham & Women’s Hospital in Boston and Harvard Medical School have identified a policy with at least $100 million in potential savings: make generic substitution policies work more effectively.

A new study in the July issue of Health Affairs highlights savings opportunities some state Medicaid programs could take advantage of by changing their generic substitution laws.  Currently, 39 state programs require patient consent for pharmacists to substitute a prescribed brand name drug for a generic.

Given the strong influence of pharmaceutical marketing, patients often have an unwarranted negative view of generic drugs, requesting more expensive branded options when they are not necessary.  Generics are certified by the FDA to be chemically equivalent to their brand name counterparts.  The rationale for allowing pharmacists to voluntarily substitute generics is to ensure that Medicaid is not wasting money.  Saving money protects access to care in budget-stressed programs like Medicaid.   By leaving the generic substitution decision to pharmacists, states could expect to save more than $100 million on just three top-selling medications—Plavix, Lipitor and Zyprexa— that are nearing patent expiration.

The study, led by Dr. William H. Shrank, looked at the relationship between Medicaid policies on generic substitution and the use of the cholesterol drug simvastatin vs. Zocor, its branded equivalent, after Zocor’s patent expired in June 2006.  While all states have adopted generic substitution laws, the extent to which pharmacists or patients can influence the medications they choose differs from state to state.  The Harvard researchers found that states that did not require patient consent to switch prescriptions from Zocor to the clinically equivalent, less costly simvastatin saved $15.35 per prescription on these medications in the first quarter after patent expiration.  If all states had adopted such policies, Medicaid programs could have saved $19.8 million nationwide on the introduction of simvastatin.

While patients should be empowered to participate in their own health decisions, this study demonstrates that requiring patient consent for generic substitution impedes patients from initially choosing generics even when they will eventually prefer them to the brand name.  After four financial quarters, the rates of choosing generic simvastatin over Zocor begin to converge between states that require consent and states that do not.  Patients in both states will eventually choose to take advantage of the cost savings from choosing the safe, effective, and cheaper alternative.  But for patients in states that do require consent, the cost savings come at a slower pace.  And in the case of Zocor, that meant $19.8 million in foregone savings for state Medicaid programs—savings that could have been used to protect access to care.

The study comes as welcome news for patients and policy makers at a time when state Medicaid programs are facing severe budget cuts.  Generics cost, on average, 30-80 percent less than brand name competitors.

Marcia Hams, director of prescription access and quality at Community Catalyst, stressed the great importance of these findings in light of Medicaid shortfalls in a recent BNA report.  If state programs are forced to overspend on drugs, she explained, people may  start to lose their benefits or eligibility.  The use of brand name drugs instead of generics is thus “an unnecessary cost that could endanger beneficiaries in the [Medicaid] program.”

Massachusetts Medicaid, with a very high (78 percent) generic rate and no patient consent requirement, may illustrate the point, according to Hams, although other strategies were also involved. “A study we commissioned in 2009 found that MassHealth achieved significant savings to curb increasing drug costs by using coordinated policies that increased generic drug use, while putting clinical considerations first.”

Of course, neither PostScript nor the study authors are advocating the use of generic medication for every patient or for the use of generic-only formularies.  A physician should, and can, always mandate the use of a brand name drug if necessary.  (Find out more information on the safety, value, and appropriate use of generic medications at: http://www.genericsarepowerful.org/). We agree with the study authors that a modified generic substitution policy could produce cost savings without compromising quality while leaving room to invest health care dollars more effectively and preserve vital programs.

–Joy Lee, policy intern

Two recent headlines highlight the need for a federal electronic track-and-trace system for prescription drugs.

Last week, a Baltimore pharmacist was sentenced to 57 months in prison for making fraudulent claims and misbranding hundreds of thousands of bottles of drugs from an unlicensed supplier. According to the FDA Office of Criminal Investigations, an inspection in 2008 revealed more than 200,000 bottles of misbranded drugs in Pamela Arrey’s Medicine Shoppe, as well as drugs that had expired, or had altered labels. Arrey’s rebranding schemes included metformin, a diabetes medication, and gabapentin, an anti-seizure medication.  (See the FDA press release here.)

And FiercePharma has just released its Top Ten list of pharma cargo thefts by value in 2009-2010. Atop the list was March’s headline-making $76 million heist of antidepressants and other drugs through the roof of an Eli Lilly plant in Connecticut. But it is only the most high-profile case in a growing trend: Pharmaceutical cargo theft has quadrupled in the last four years, according to Freightwatch International, which tracks cargo theft issues.

FiercePharma’s list and Arrey’s conviction are reminders of the risks posed to patients when improperly sold or stolen pharmaceuticals end up back on pharmacy shelves.

Cargo theft and misbranding schemes like Arrey’s highlight the need for a federal electronic track-and-trace system, which would establish a unique electronic ID tag for each medicine bottle so that drugs can be traced back to their original source and verified at each transaction point along the supply chain, from the factory to the pharmacy shelf.  Congresswoman Rosa Delauro (D-CT), who chairs the House subcommittee on FDA appropriations, emphasized the importance of such a system in her Chairman’s Mark last week, and federal track and trace legislation has been introduced in previous sessions of Congress.

For more on drug safety and the importance of developing a prescription drug tracking system, visit the Pew Prescription Project’s Securing a Safe Drug Supply.

–Kate Petersen, PostScript blogger

Yesterday we blogged about comments Prescription Access Litigation and others made to the FDA in support of proposed rules on presenting risk information in broadcast drug ads.

Numerous other consumer and public health groups have commented, and overall offered resounding support for these proposed regs. The Patient, Consumer and Public Health Coalition offered their support for these regulations and stressed that “the goal of DTC ads is to persuade, not to educate, and so DTC ads emphasize the benefits but not the risks of prescription drugs.”

Consumer groups, including the National Consumers League, additionally offered support for the proposed fifth requirement of dual-modality, simultaneous audio and textual presentation. Consumers Union voiced the importance of dual-modality in their comment stating that “[p]roviding an audio warning with other things happening in the background is, no matter how hard one tries, distracting” and, “[p]roviding a text warning while talking about other things is distracting;” “Providing the same, simultaneous audio and visual warning is the single best way to make a lasting impression that will be helpful to patient-consumers.”

Some consumer groups also argued that pre-review of ads should be required. Here’s Public Citizen: “to obtain approval of DTC advertising on broadcast media, a party shall present market research demonstrating that information concerning side effects, contraindications and warnings is comprehensible to the target audience.” A pharmacists group and pharmaceutical powerhouse Eli Lilly also supported the use of focus groups to review and “pre-approve” ads and to pilot test that elements (e.g. font size, color, placement) of an ad.

In addition to these shared themes, AARP also suggested that the FDA rule should specify where in the ad the “major statement” should appear” and that the major statement should not be allowed to be placed in the middle of the ad “where it can be bookended by conveyance of benefit information and is least likely to be retained by consumers.”

The two pharmacist organizations that commented–the American Society of Health-System Pharmacists and the Academy of Managed Care Pharmacy (AMCP)—supported the new proposed rules, as well as dual modality in ads and pre-dissemination review whether by the FDA or by consumer test groups.

Industry against dual modality, for delays
Industry was relatively quiet on these new proposed regulations:  only the Pharmaceutical Research and Manufacturers of America (PhRMA) and four pharmaceutical companies submitted comments so far. Though industry all stressed the public health benefits of DTCA and generally offer their support for the FDA’s action to further clarify the standards, a few common themes of opposition are apparent in all industry comments.

On the whole, industry seems very opposed to the proposed fifth standard of requiring dual modality. Sepracor argues that dual modality “could prove to complicate the presentation for consumers.” PhRMA seconded this argument and said that “dual modality might produce presentations that actually overemphasize risk information.”

Merck further stated that dual modality “does not improve consumer recall or understanding of important risks information.” Though Merck supported this argument with one 2005 study, it went on to mention the limitations of this study and none of the other industry commenters provided any support for their arguments against dual modality, and all of industry’s comments against dual modality ignore the numerous studies that have shown that the technique enhances clarity and recall of information (and which the FDA cited in its proposed rule).

The second overarching theme of the industry comments seems to be an attempt to delay the implementation of these rules. Sepracor, Merck and Eli Lilly all suggest that the FDA do further research and analysis on these standards before implementation. Sepracor argued that the rule should not be made effective until the results of FDA’s study on the impact of distraction can be published and commented on.

This argument reads largely as a delay tactic employed by Sepracor to postpone the inevitable implementation of this rule. Though there is no doubt that the FDA’s study may help them to further understand what elements of broadcast media can be distracting, there’s little debate that the impact of distraction on consumer understanding… is to distract, and that’s hardly a reason for FDA to delay implementing these rules when the public’s health is at stake.

In one of the more head-scratching unsupported assertions, Sepracor stated that up to 70 percent of the time slot of an ad is used to convey safety information for the drug. Anyone who’s ever viewed one of the numerous DTC ads currently on TV knows that this statistic has little foundation in reality.

–Emily Cutrell, Prescription Access Litigation

(This is the first in a two-part blog. Read tomorrow when we look at how industry and other stakeholders weighed in.)

How clear does risk information need to be in direct-to-consumer drug ads? That’s the question the FDA is getting closer to answering as stakeholders weighed in this week on the agency’s proposed rules for presenting risk in broadcast ads.

Twenty-two members (see end of the blog for a complete list) of Community Catalyst’s Prescription Access Litigation Coalition and other supporting groups joined PAL in submitting comments that support the agency’s new proposal to make risk information clear, conspicuous, and neutral in TV ads. The groups also suggested the FDA require that risks be quantified in ads and that the overly-scientific talk be toned down to match the comprehension of the viewer who would have the most trouble understanding the ad.

Many of the provisions in this year’s proposed rule do reinforce the handling of risk information that FDA proposed in last year’s draft guidance. But they are clearer and more concrete, and would go further than the agency’s current standard of “fair balance,” in which drugmakers are only required to present risk as clearly as they present benefits. Specifically, the proposed rules would require that ads use everyday language that is easily readable when in writing and is presented slow enough and prominent enough, whether in writing or audio form, to be easily understood by a consumer viewing the ad. The FDA also proposed a rule that would ban any distracting sounds or images in broadcast prescription drug advertisements.

A step back on why all this matters: remember that the U.S. is one of only two countries that allows drugs to be advertised on TV at all (New Zealand is the other).  And it’s a relatively recent allowance—only in 1997 did the loosening of an FDA regulation about how the major statement about a drug is presented open the floodgates to the sleep butterflies, allergy bees, and PMS symptom balloons.

As was shown by the PAL cases on Vytorin-Zetia, Nexium, Vioxx and Ketek, those changes came with controversy and human costs. Rofecoxib, or Vioxx, was heavily advertised to consumers and physicians in its first year before it was pulled from market after being linked to between 35,200 to 52,800 deaths and 88,000 to 140,000 heart attacks in the US. This caused the Institute of Medicine and other experts to call for an end to DTCA for new drugs, whose side effects are often not known (or in Vioxx’s case, suppressed) until years after they appear on the market.

The link between DTCA and increased prescribing of newer, less-tested drugs has been well-documented, and policymakers, regulators and academics have all expressed concern that the FDA’s inability to regulate and oversee broadcast ads has put the public’s health at unnecessary risk.

But despite this concern and growing evidence that drug ads carry risks beyond the speed-read ones, drug companies came up short on proving public health benefits to their current ad style or offering new evidence-based ideas for presenting risk info in a clear and neutral way. We’ll take a look at what they said tomorrow. Short of all out banning DTCA, the FDA must determine the appropriate standards to best protect the public.

What else could the FDA do?
In addition to offering support to the proposed rules, PAL suggested additional steps that could further enhance the clarity of ads and thus further protect consumers. PAL urged the FDA to address the widely-held myths that the FDA approves all TV ads, and that the government only lets drugs that are “really safe” be advertised on TV, by requiring a disclaimer that “FDA has not approved this ad” for all ads that have not been pre-approved, and including the adverse event hot-line “Medwatch” number in all TV ads.

Though PAL fully supports FDA’s increased vigilance in regulating prescription drug ads, we noted in our comments that there are far more new ads being produced than there are FDA staff members to review these ads. It’s a big imbalance, and though increased funding and staffing of the FDA would help, delayed warning letters that appear long after an ad-buy—such as this Lunesta one–will probably still happen.

To address this issue, the FDA should start using their authority to fine drug companies for ads that violate FDA regulations. Though fining will not increase the speed at which the FDA is able to review ads, it could potentially increase pharma’s compliance with these regulations and exact a price from noncompliant companies, even if the ad in question is no longer being aired.

Those joining Community Catalyst’s and PAL’s comments were:

The Alliance for Retired Americans
The American Federation of State, County and Municipal Employees (AFSCME)
The American Medical Student Association (AMSA)
Breast Cancer Action
California Alliance for Retired Americans (CARA)
CALPIRG
The Coalition of Wisconsin Aging Groups
Connecticut Center for Patient Safety
Connecticut Citizen Action Group
Consumers Advancing Patient Safety (CAPS)
Health Care for All
IUOE Local 4 Funds
Long Island Health Access Monitoring Project
MASSPIRG
New England Carpenters Health Fund
National Legislative Association on Prescription Drug Prices (NLARx)VPIRG
National Women’s Health Network
Oregon Health Action Campaign
Prescription Policy Choices
TeamstersCare
US PIRG

–Emily Cutrell, Prescription Access Litigation

A new survey of physicians published in the JAMA Archives of Surgery this week suggests that across specialties, the majority of physicians still hold a positive attitude about gifts and meals from pharmaceutical and medical device companies.

Confirming what previous studies on marketing influence have found, cognitive dissonance was at work here: the majority of the 590 respondents (52.2 percent), who worked at Mount Sinai School of Medicine and its affiliated hospitals, believed that receiving industry gifts and meals influenced other physicians’ prescribing, but just about one-third believed that they themselves were influenced by gifts and meals. Earlier studies quantifying physician attitudes have suggested an even greater differential.

And though the majority of respondents thought that industry funding of medical education was acceptable, more than two-thirds of them perceived bias in such sponsored lectures.

The researchers hypothesized that surgeons, whose journals had published little of the literature to date on gifts’ prescribing influence, would have more favorable views of industry gifts and involvement in medical education. The results bore this out, with surgeons significantly more amenable to certain types of gifts, and industry funding of medical school programs (82.8 percent compared to 71.1 percent overall). Recent news stories in Bloomberg and the New York Times have revealed the unique coziness between some high-profile surgeons and makers of implants and devices that failed their patients.

In an interesting aside, the specialty most likely to say that its institution should prohibit residents, students and attendings from interacting with pharma and device reps were psychiatrists, who have been the focus of a series of headlining Congressional investigations in recent years and have consequently done a lot of work to clean their house.

So where is education and awareness in all this? In many cases, the more familiar a physician was with her institution’s guidelines, the less likely she was to rate gifts and meals as appropriate or very appropriate, and the less likely she was to say that samples improve patient care.

But just over half of the respondents surveyed said they were familiar with their institution’s guidelines–guidelines, we note, that received an “A” on the American Medical Student Association 2009 Scorecard. One question then is: How are the many institutions that have strengthened or developed new policies communicating them to their clinicians – or are they?

The authors suggest that despite such policy changes, the medical practice environment still fosters a “hidden curriculum” that approves of industry gifts, meals and relationships–a curriculum that has left physicians behind the public and regulatory movement toward trimming marketing’s influence on medicine.

Despite this sea change in public and governmental attitudes during the last several years, the physicians we surveyed retain generally positive attitudes toward many industry gifts, and more than two-thirds still find gifts and lunches from industry acceptable. In fact, our findings are remarkably similar to results of other studies of physician attitudes toward industry from as early as 2001….

The positive attitudes of physicians we surveyed are likely to reflect the continuing acceptability of industry interactions and gifts within the culture of medicine despite changing guidelines. Physicians in practice continue to speak frequently with industry representatives, and academic physicians enjoy food and other industry gifts when they attend continuing medical educational events and national specialty meetings. Although other groups have found that education about the effect of industry contact may have a modest effect on physician attitudes, physician attitudes are not likely to align with those of the public until the culture of medicine rejects industry marketing interactions more fully.

–Kate Petersen, PostScript blogger